Inclusion Criteria:
* The subjects volunteered to join the study and signed informed consent, with good compliance and follow-up.
* Patients with histologically or cytologically confirmed non-MSI-H ( according to the detection criteria of the institutional testing center, immunohistochemistry, PCR or NGS detection can be used ) unresectable advanced colorectal cancer with liver metastasis ;
* Age ≥ 18 years, ≤75 years， male or female ;
* ECOG PS 0-1;
* Expected overall survival ≥3 months
* Patients must have at least one measurable liver metastases (RECIST 1.1)
* Patients who had only received one standard first-line systemic treatment and were confirmed to be ineffective, or could not tolerate first-line treatment ;
* Patients must have adequate organ and bone marrow function( No blood components and cell growth factors were used within 14 days before enrollment )
* Male or female patients with fertility voluntarily used effective contraceptive methods, such as double-barrier contraceptive methods, condoms, oral or injectable contraceptives, intrauterine devices, etc., during the study period and within 6 months of treatment in the last study. All female patients will be considered to have fertility, unless the female patient has natural menopause, artificial menopause or sterilization ( such as hysterectomy, bilateral adnexectomy or radioactive ovarian irradiation, etc. ), otherwise the female patient 's serum or urine test showed no pregnancy within 7 days before the study, and must be non-lactating patients.
Exclusion Criteria:
* Patients who are allergic or suspected to be allergic to the study drug or similar drugs
* Patients had other malignant tumors in the past 5 years or at the same time (except for the cured skin basal cell carcinoma and cervical carcinoma in situ);
* Participating in other clinical trials and received at least one treatment within 4 weeks before enrollment
* Patients with autoimmune disease or history of autoimmune disease within 4 weeks before enrollment
* patients currently have central nervous system (CNS) metastasis or previous brain metastasis and the symptom control time is less than 2 months
* Patients cannot take fruquintinib orally
* Patients who have received organ transplantation and bone marrow transplantation in the past
* Have taken other strong inducers or inhibitors of CYP3A4, P-gp substrates and BCRP substrates within 2 weeks before the First medication
* Received any operation (except biopsy) or invasive treatment or operation (except venous catheterization, puncture and drainage, etc.) within 4 weeks before enrollment
* Pleural effusion or ascites causing relevant clinical symptoms, including respiratory syndrome (dyspnea≥CTC AE grade 2)
* Clinically significant electrolyte abnormality#
* Systolic blood pressure \> 140mmHg or diastolic blood pressure \> 90mmHg regardless of any antihypertensive drugs; Or patients need more than two antihypertensive drugs
* Proteinuria ≥ 2+ (1.0g/24hr);
* Active gastric and duodenal ulcer, ulcerative colitis or uncontrolled hemorrhage in GI, or other conditions that may cause GI bleeding and perforation as determined by the investigator;
* Have evidence or history of bleeding tendency within 3 months or thromboembolic events within 12 months before enrollment( Hemorrhage \> 30 mL within 3 months, hematemesis, black feces, hematochezia ), hemoptysis ( fresh blood \> 5 mL within 4 weeks ) or thromboembolic events ( including stroke events and / or transient ischemic attack ) within 12 months ;
* Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina pectoris or coronary artery bypass grafting within 6 months before enrollment; NYHA classification \> 2 Grade; ventricular arrhythmia requiring medical therapy; ECG showing QTc interval ≥ 480 ms
* Active or uncontrolled serious infection (≥CTCAE grade 2 infection)
* Pregnant or lactating women
* Any other disease, with clinically significant metabolic abnormalities, physical examination abnormalities or laboratory abnormalities, according to the judgment of investigator that the patient is not suitable for the the study drug (such as having epileptic seizures and require treatment), or would affect the interpretation of study results, or put patients at high risk
* Clinical uncontrolled active infections, including human immunodeficiency virus (HIV) infection, active hepatitis B / C (HBV DNA Positive\[1×104 copies/mL or \>2000 IU/ml\], HCV RNA positive\[\>1×103 copies/mL\]);
* Patients have other factors that may affect the results of the study or cause the study to be terminated halfway, such as alcoholism, drug abuse, other serious diseases (including mental diseases) that require concomitant treatment, and serious laboratory abnormalities. Accompanied by family or social factors, which will affect the safety of patients.
