Inclusion Criteria:
* Male or female that must have signed a written informed consent prior to any study specific procedures
* Aged ≥ 18 years at randomization
* Patient with histologically proven metastatic colorectal cancer previously treated for metastatic disease by chemotherapy treatment including oxaliplatin, irinotecan, fluoropyrimidine, antiangiogenic (anti-VEGF: bevacizumab or aflibercept) and anti-EGFR (cetuximab or panitumumab) if indicated (MSI tumor could be included if previously pretreated with anti PD1/PDL1 therapy) n.b:
* a patient treated with oxaliplatin in a neoadjuvant/adjuvant situation with a recurrence of the disease within 6 months following the last administration is considered resistant to oxaliplatin and validates the criterion if no administration of oxaliplatin has been carried out in a metastatic disease situation.
* exception for VEGF if medically contraindicated during previous metastatic disease treatment (should be clearly documented in the disease history of the patient) it is allowed to included the patient with or without Bevacizumab.
* Have a performance status of 0 or 1 according to the WHO Easter Cooperative Oncology Group (ECOG)
* Knowledge of RAS, BRAF, Microsatellite status
* Baseline tumoral evaluation (thoraco-abdomino-pelvic computed tomography) perfromed within 21 days before randomization with at least one measurable lesion according to RECIST 1.1 criteria.
* Patient willing and able to comply with protocol for the duration of the study including: scheduled visits and exams, visits during the follow-up and treatment compliance.
* Adequat hepatic, renal and bone marrow function within the following limits:
* Total bilirubin ≤ 1,5 times the upper limit of normal (ULN) (unless documented Gilbert's syndrome);
* ASAT et ALAT ≤ 5 times ULN;
* Measured Creatinine clearance (Cockcroft and Gault) \> 30 ml / min
* Absolute Neutrophil Count (ANC) \> 1,5. 109 / L;
* Platelet count ≥ 150. 109 / L;
* Haemoglobin ≥ 9 g / dL (patients can be included even if they have been transfused)
* Albuminemia ≥ 30 g / L;
* Negative Hepatitis B, C and HIV serologies, or absence of active B or C hepatitis
* Urea protein, urine dipstick should be less than 2 crossese and/or 24 hour proteinuria ≤ 1g/24h
* Availability of tumor material dated less than 5 years with sufficient quantity (15 to 20 whithe slides) and quality (Good morphological conservation / Presence of tumor tissue / Histopathology consistent with the indication / More than 100 tumor cells)
* Patient must be affiliated to a social health insurance
* Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients (urine within 72h or serum pregnancy within 14 days prior to inclusion).
* Women of childbearing potential willing to use adequate contraception method (including the use of a mechanical method of contraception in the event of hormonal contraceptive treatment) during the treatment period and 6 months following the end of treatment.
* Male patients with a partner of childbearing potential should use effective contraception during treatment and for up to 6 months after stopping treatment.
* Normal ECG or ECG without clinically significant findings with QTcF \< 470 ms.
Exclusion Criteria:
* Other concurrent malignancies the last 3 years, except adequately treated cone-biopsied in situ carcinoma (as per exemple of the cervix, basal cell, squamous cell carcinoma of the skin, low risk prostate cancer or other insitu carcinoma juged eligible according the coordinator). Patient who have had potentially curative therapy for a prior malignancy are eligible provided there has been no evidence of disease for ≥ 3 years and the risk of recurrence is considered low.
* Symptomatic brain metastases
* Estimated prognosis \<3 months.
* Mutational status BRAF mutant (V600E only)
* Participation in progress, or in the 30 days preceding the first scheduled day of dosing in this study, in another therapeutic trial with an experimental molecule or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer.
* Severe unbalanced illness, underlying infection that may prevent the patient from receiving treatment. Patients with a clinically important and unresolved Grade 3 or 4 non-haematologic adverse reaction related to previous therapies. Also participant with any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted \> 4 weeks and was related to the most recent treatment.
* Bowel obstruction or sub-obstruction or a history of inflammatory bowel disease or significant gasto intestinal disorder
* History of autoimmune or inflammatory disease or interstitial lung disease.
* Patient with congenital galactosemia, total lactase deficiency (lactose intolerance) or glucose-galactose malabsorption syndrome
* Severe arterial thromboembolic events less than 6 months before randomization
* New York Heart Association (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure (defined as ≥ 160/100 mm Hg)
* Clinically significant decrease in performance status (medical records) within 2 weeks of intended first dose administration.
* -Contraindication to receive a treatment with trifluridine/tipiracil or an anti-IL-1α (XB2001 True Human antibody) and/or patient already treated by trifluridine/tipiracil, or an anti-IL-1α.
* Concomitant systemic treatment with immunotherapy, immunosuppressants, corticosteroid therapy ≥ 10 mg equivalent prednisone/prednisolone or hormone therapy: corticosteroid therapy administered chronically, immunosuppressive treatment, biotherapy administered as part of the management of an inflammatory disease (anti-TNF, anti-IL6, anti-IL1, anti PD-1, anti EGFR etc.) and live virus vaccines administered up to 14 days prior the first scheduled dose of treatement administration.
* Current pregnancy (mandatory pregnancy test at baseline for female of childbearing potential) or breastfeeding.
* Patient with any psychiatric, psychological, sociological, geographical problem or other severe concomitant disease, disorder or condition that potentially compromising the understanding of the information, the safety of the patient, the interpretation of study results or the conduct of the study compliance with the study protocol and follow-up schedule.
* Patient deprived of their liberty or under guardianship, curatorship or safeguard of justice.
* Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution. Presence or suspicion of active bacterial, fungal or viral infections, or uncontrolled fever.
* Major surgery within 2 weeks prior to randomization or have an unhealed operation wounds.
