Fruquintinib Versus Bevacizumab Plus Chemotherapy in Second-Line RAS-Mutant Metastatic Colorectal Cancer (FRU-RAS)

Inclusion Criteria: 1. Patients voluntarily participate in the study, sign the informed consent form, and have good compliance. 2. 18 years ≤ age ≤ 75 years. 3. Histologically and/or cytologically confirmed unresectable metastatic colorectal cancer. 4. RAS mutant type. 5. Previously received chemotherapy based on fluoropyrimidines (5-fluorouracil or capecitabine, etc.), oxaliplatin or irinotecan; previous adjuvant/neoadjuvant therapy is allowed. If recurrence or metastasis occurs during or within 6 months after adjuvant/neoadjuvant therapy, it is considered as the failure of first-line systemic chemotherapy for advanced disease. 6. Patients must have at least one measurable lesion (RECIST 1.1). 7. ECOG performance status 0-1. 8. Expected survival ≥ 12 weeks. 9. Blood tests (without blood transfusion within 14 days) 1) Absolute neutrophil count ≥ 1.5×10\^9/L, platelet count ≥ 100×10\^9/L, hemoglobin concentration ≥ 9g/dL; 2) Liver function tests (AST and ALT ≤ 2.5×ULN, bilirubin ≤ 1.5×ULN; if there is liver metastasis, AST and ALT ≤ 5×ULN); 3) Renal function (serum creatinine (Cr) ≤ 1.5×ULN, or creatinine clearance rate (CCr) ≥ 60ml/min); 4) Coagulation, international normalized ratio (INR) ≤ 1.5×ULN, prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5×ULN; 5) Thyroid function, thyroid stimulating hormone (TSH) ≤ upper limit of normal (ULN); if abnormal, FT3 and FT4 levels should be examined, and patients with normal FT3 and FT4 levels can be included. 10. Women of childbearing age are willing to use medically approved effective contraceptive measures (such as intrauterine devices, contraceptives or condoms) during the study and for 3 months after the last administration of the study drug; for male subjects whose partners are of childbearing age, it is recommended to take effective contraceptive measures during the study and for 3 months after the last administration of the study drug. Exclusion Criteria: 1. Enrolled in another clinical study within the 4 weeks prior to enrollment in this study; 2. Previously received anti-angiogenic small molecule targeted drug treatment, such as fruquintinib, etc.; 3. Symptomatic brain or leptomeningeal metastases (except for those who have undergone local radiotherapy or surgery for brain metastases for more than 6 months and have stable disease control); 4. Experienced severe infection within 4 weeks prior to enrollment (e.g., requiring intravenous infusion of antibiotics, antifungal drugs, or antiviral drugs); 5. Hypertension that cannot be well controlled with antihypertensive drugs (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg); 6. Had active bleeding or coagulation disorders within 2 months prior to enrollment, had a bleeding tendency or was receiving thrombolytic therapy, and was assessed by the investigator as unsuitable for enrollment; 7. Had active heart disease within 6 months prior to treatment, including myocardial infarction, severe/unstable angina pectoris. Echocardiography showed left ventricular ejection fraction \< 50%, or had poorly controlled arrhythmia; 8. Had other malignant tumors within 5 years prior to enrollment or at the same time (except for cured basal cell carcinoma of the skin and cervical carcinoma in situ); 9. Known to be allergic to the study drug or any of its excipients; 10. Unable to take oral medication or the investigator judged that the subject had a condition that affected drug absorption; 11. Pregnant (positive pregnancy test before medication) or breastfeeding women; 12. Had active or uncontrolled severe infections 1) Known human immunodeficiency virus (HIV) infection; 2) Known history of clinically significant liver disease, including viral hepatitis \[known hepatitis B virus (HBV) carriers must be excluded from active HBV infection, i.e., HBV DNA positive (\>1×10\^4 copies/mL or \>2000 IU/mL); 3) Known hepatitis C virus (HCV) infection and HCV RNA positive (\>1×10\^3 copies/mL), or other hepatitis, liver cirrhosis; 13. Urinalysis indicated proteinuria ≥ 2+, and 24-hour urine protein quantification \> 1.0g; 14. Other situations judged by the investigator as unsuitable for inclusion in this study.