The Safety and Efficacy of HAIC+Tislelizumab+Regorafenib in Patients With Colorectal Liver Metastases

Inclusion Criteria: 1. Age≥18 years old 2. Histologically or cytologically confirmed colorectal cancer with unresectable or surgical contraindicated liver metastases * Extrahepatic metastases are allowed and the primary tumor load is assessed to be intrahepatic by two or more attending physicians * Whether liver metastases can be resected or not is determined by two or more attending physicians according to the Chinese guidelines for the diagnosis and comprehensive treatment of colorectal liver metastases 3. Patients with unresectable colorectal liver metastases after failed standard second-line therapy * Including, but not limited to, Oxaliplatin, Fluorouracil, and Irinotecan * Treatment failure is defined as disease progression and intolerable toxicity 4. Patients who withdrew from standard therapy due to unacceptable toxicity, guaranteed to discontinue treatment before disease progression and excluded treatment with the same drug, are also allowed to be included in the study. 5. At least one measurable lesion according to RECIST 1.1 criteria 6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 7. Subject life expectancy ≥12 weeks 8. Laboratory tests of bone marrow, hepatic and renal function and coagulation function within 7 days before the first dose of medication meet the study requirements \- No blood transfusion, blood products, or correction with granulocyte colony-stimulating factor or other hematopoietic stimulating factor within 7 days before laboratory testing. 9. Female patients of childbearing age must have a negative blood pregnancy test within 7 days before the first dose of medication and male or female patients of childbearing age volunteered to take effective contraceptive measures during the whole treatment and within 3 months after treatment 10. All patients must sign an informed consent form and follow the trial treatment protocol and follow up plan Exclusion Criteria: 1. ANC \<1.5×109/L, or platelet count \<80×109/L, or HGB \< 9g/dL; \- Blood transfusion to meet enrollment criteria within 2 weeks before enrollment is not allowed 2. serum total bilirubin\>2.0 times upper limit of normal 3. AST and/or ALT\>5.0 times upper limit of normal 4. Serum creatinine\>1.5 times upper limit of normal, or creatinine clearance rate\<50ml/min(calculated according to the Cockcroft-Gault formula) 5. APTT or PT\>1.5 times upper limit of normal 6. Clinically significant severe electrolyte abnormalities by the investigator 7. Urine protein test 2+ or more, or 24 hours urine protein quantitation ≥1.0g/24h 8. Hypertension that is not stably controlled by medications: systolic blood pressure(SBP) \>140mmHg or diastolic blood pressure(DBP) \> 90mmHg 9. Patients with active gastric and duodenal ulcer, ulcerative colitis or other gastrointestinal diseases or unresected tumors with active bleeding, or other conditions that may cause gastrointestinal bleeding or perforation as judged by the investigators; Or patients with previous gastrointestinal perforation or gastrointestinal fistula, which is not cured after surgical treatment 10. History of arterial or deep-vein thrombosis within 6 months before enrollment or evidence or history of bleeding tendency within 2 months before enrollment, regardless of severity 11. History of troke or transient ischemic attack within 12 months before enrollment 12. History of heart disease within 6 months before enrollment, manifested as congestive heart failure, acute myocardial infarction, severe/unstable angina, coronary artery bypass grafting; impaired cardiac function in NYHA class 2 or above; left ventricular ejection fraction (LVEF) \<50% 13. Uncontrolled malignant pleural, ascites, or pericardial effusion \- defined as not being effectively controlled with diuretics or punctures 14. Clinically detectable second primary malignancy or history of other malignancies within 5 years. Adequately treated nonmelanoma skin cancers, cervical carcinoma in situ, and superficial bladder tumors \[noninvasive tumors, carcinoma in situ, and T1 (tumor invasion of the lamina propria)\] are excluded 15. Central nervous system (CNS) metastases or previous brain metastases 16. Clinically uncontrolled severe active infection 17. Pregnant or lactating women or women of childbearing age have a positive pregnancy test before the first dose of medication; Or female participants themselves and their partners who are unwilling to use strict contraception during the trial 18. Patients are considered by the investigator to have any clinical or laboratory abnormalities or compliance issues that precluded participation in the trial 19. Serious psychological or psychiatric abnormalities