Inclusion Criteria:
* 1\. Age ranged from 18 to 75 years old (inclusive), regardless of gender;
* 2\. Pathological diagnosis as metastatic colorectal adenocarcinoma, with RAS and BRAF wild-type and non-dMMR/MSI-H;
* 3\. Tumor tissue available for central laboratory testing;
* 4\. Metastatic colorectal cancer with disease progression after 2nd line treatment; previously received standard chemotherapy based on fluorouracil, oxaliplatin, irinotecan; patients are allowed to previously receive EGFR and/or VEGF inhibitors, but not allowed to previously receive regorafenib, fruquintinib;
* 5\. Measurable disease according to RECIST1.1;
* 6\. Eastern Cooperative Oncology Group (ECOG) score 0-1 points;
* 7\. Life expectancy ≥3 months
* 8\. Adequate main organs and bone marrow function.
* 9\. Patients must give informed consent to this study before the experiment and voluntarily sign a written informed consent form.
Exclusion Criteria:
* 1\. Participants who have been systematically treated with an EGFR inhibitor (such as cetuximab) within 4 months prior to the first dose of study drug.
* 2\. Central nervous system metastasis or meningeal metastasis;
* 3\. Patients with high risk of bleeding due to tumor invasion of important arteries;
* 4\. Uncontrolled or requiring repeated drainage of pleural effusion, pericardial effusion, or abdominal effusion;
* 5\. The adverse reactions of previous anti-tumor treatments (including radiotherapy) have not yet recovered to CTCAE 5.0 evaluation ≤ level 1;
* 6\. Diagnosed as a second primary malignant tumor within 5 years prior to the first administration of the study drug;
* 7\. Have received anti-tumor treatments such as chemotherapy, biological therapy, targeted therapy, etc. within 21 days before the first dose of the study drug; radiotherapy within 2 weeks before the first dose of the study drug; Chinese medicine or Chinese patent medicine with anti-tumor effect within 1 week before the first dose of the study drug;
* 8\. Have received a live viral vaccine or live-attenuated vaccine within 28 days before the first dose of study drug or plan to receive it during the study;
* 9\. Use of immunosuppressive medications within 14 days prior to the first dose of study drug;
* 10\. Those who use strong CYP3A4 inducers within 14 days before the first administration of the study drug, or those who use strong CYP3A4 inhibitors or strong UGT1A9 inhibitors within 2 week, or those who cannot suspend the use of the above drugs during the study;
* 11\. Have received radiation therapy or other localized palliative treatment within 14 days before the first dose of study drug;
* 12\. Have undergone major surgery (excluding needle biopsy) or suffered severe traumatic injury within 28 days before the first dose of study drug;
* 13\. Have a history of serious cardiovascular disease;
* 14\. Previous or current presence of interstitial pneumonia/lung disease;
* 15\. History of autoimmune diseases;
* 16\. A history of immunodeficiency, including HIV testing positive, or having other acquired or congenital immunodeficiency diseases, or having a history of organ transplantation;
* 17\. Have infectious diseases requiring systemic anti-infective treatment;
* 18\. Active hepatitis B; hepatitis C infection; syphilis infection, active tuberculosis;
* 19\. Known presence of hypersensitivity or intolerance to any component of EGFR monoclonal antibody, irinotecan hydrochloride injection, regorafenib and its excipients;
* 20\. Women during lactation or pregnancy; women with fertility tested positive for blood pregnancy within 7 days prior to enrollment in the trial;
* 21\. Any male and female patients with fertility who refuse to use effective contraceptive methods throughout the entire trial period and within six months after the last administration;
* 22\. Other conditions that, in the opinion of the investigator, may affect the safety or compliance of drug treatment in this study, including but not limited to: psychiatric disorders, any severe or uncontrollable diseases, etc.
