A Prospective Multi-centered Randomized Controlled Trial on Fruquintinib in Combination With HAIC in the Treatment of Liver Metastatic Colorectal Cancer After Failure of Second-line Systematic Therapy

Inclusion Criteria: 1. Fully understand the study and voluntarily sign the informed consent form; 2. Age ≥ 18 years; 3. Patients with unresectable colorectal liver metastases who have failed standard second-line systemic therapy, who have not previously received HAIC therapy, and have not received third-line standard targeted agents (regorafenib or fruquintinib or trifluridine tipiracil (TAS-102); 4. Definition of liver metastases: at least 1 measurable liver metastasis lesion (based on RECIST 1.1); if the liver metastases are single, the tumor is \> 5 cm; if multiple tumors, it needs to be greater than or equal to 4, of which at least 1 exceeds 3 cm; 5. PFS \> 4 months from last dose of oxaliplatin with FOLFOX regimen 6. Child-Pugh classification of liver function: A; 7. ECOG performance status 0-1, and no deterioration within 7 days; 8. BMI ≥ 18; 9. Expected survival ≥ 3 months; 10. Vital organs function in accordance with the following requirements (any blood components and cell growth factors are not allowed within 14 days before enrollment): * Absolute neutrophil count ≥ 1.5 × 109/L and white blood cells ≥ 4.0 × 109/L; * Platelets ≥ 100 × 109/L; * Hemoglobin ≥ 90 g/L; * Total bilirubin TBIL ≤ 1.5 times ULN; * ALT and AST ≤ 5 times ULN; * Urea nitrogen/urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN (and creatinine clearance (CCr) ≥ 50 mL/min); * Left ventricular ejection fraction (LVEF) ≥ 50%; * Fridericia-corrected QT interval (QTcF) \< 470 milliseconds. * INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN. 11. women of childbearing age need to take effective contraceptive measures; 12. good compliance and cooperation with follow-up. Exclusion Criteria: 1. Unable to comply with the study protocol or study procedures; 2. Pregnant or breastfeeding women; 3. Any factor affecting oral administration; 4. Evidence of central nervous system metastases; 5. Concurrent with any of the following: uncontrolled hypertension, coronary artery disease, arrhythmia, and heart failure; 6. Alcohol or drug abuse within 4 weeks after the last clinical trial; 7. Previous VEGFR inhibition therapy; 8. Uncontrolled severe concurrent infection resulting in disability; 9. Proteinuria ≥ 2 + (1.0 g/24 h); 10. Evidence or history of bleeding tendency within 2 months prior to enrollment, regardless of seriousness; 11. Arterial/venous thromboembolic events, such as cerebrovascular accidents (including transient ischemic attack), within 12 months before the first treatment; 12. Acute myocardial infarction, acute coronary syndrome or CABG within 6 months before the first treatment; 13. Fractures or wounds that have not been cured for a long time; 14. coagulopathy, bleeding tendency or receiving anticoagulant therapy; 15. Inactivated vaccines within 4 weeks prior to enrollment or possible during the study; 16. Patients with other malignant tumors within 5 years before enrollment, except for basal cell or squamous cell carcinoma of the skin after radical resection, or cervical carcinoma in situ; 17. Active autoimmune diseases or history of autoimmune diseases within 4 weeks before enrollment; 18. Previous allogeneic bone marrow transplantation or organ transplantation; 19. Subjects who are allergic to the study drug or any of its adjuvant preparations; 20. Electrolyte abnormalities judged clinically significant by the investigator; 21. Known human immunodeficiency virus (HIV) infection. Known history of clinically significant liver disease, including viral hepatitis \[known hepatitis B virus (HBV) carriers must have excluded active HBV infection, ie, positive HBV DNA (\> 1 × 104 copies/mL or \> 2000 IU/mL); known hepatitis C virus (HCV) infection and positive HCV RNA (\> 1 × 103 copies/mL); 22. Unresolved toxicities above CTCAE v5.0 grade 1 due to any prior anticancer therapy, excluding alopecia, lymphopenia, and oxaliplatin-induced neurotoxicity ≤ grade 2; 23. Received blood transfusion therapy, blood products and hematopoietic factors, such as albumin and granulocyte colony-stimulating factor (G-CSF), within 28 days before enrollment; 24. with brain metastases, or with severe malignant pleural effusion and ascites; 25. Any other diseases, clinically significant metabolic abnormalities, physical examination abnormalities or laboratory abnormalities, according to the investigator 's judgment, there is reason to suspect that the patient has a disease or condition that is not suitable for the use of the study drug (such as having seizures and requiring treatment), or will affect the interpretation of the study results, or put the patient at high risk; 26. Patients who are considered unsuitable for inclusion in this study by the investigator.