Fruquintinib Combined With Trifluridine/Tipiracil Versus Bevacizumab Combined With Trifluridine/Tipiracil for Advanced Metastatic Colorectal Cancer

Inclusion Criteria: * Have a full understanding of this study and voluntarily sign the informed consent form; * Aged 18-75 years old (including 18 and 75 years old); * Diagnosed with advanced metastatic colorectal adenocarcinoma by histopathological examination; * Patients who have previously received first-line oxaliplatin and irinotecan treatment, or have received and failed at least two lines of standard chemotherapy regimens. These standard treatment regimens must include fluoropyrimidine-based drugs, oxaliplatin and irinotecan (with or without bevacizumab or cetuximab). Treatment failure is defined as disease progression occurring during treatment or within 3 months after the last treatment, or intolerable toxic side effects. Each line of treatment must include one or more chemotherapy drugs administered for ≥1 cycle; if recurrence or metastasis occurs during adjuvant/neoadjuvant treatment or within 6 months after completion of adjuvant/neoadjuvant treatment, the adjuvant/neoadjuvant treatment is considered a failure of first-line chemotherapy for advanced disease; * Have previously received bevacizumab treatment; * Must have at least one clear measurable lesion that meets the requirements of the Response Evaluation Criteria in Solid Tumors (RECIST 1.1); * ECOG performance status of 0-1; * Expected survival time ≥12 weeks; * Within 7 days before enrollment, the function of important organs must meet the following requirements (the use of any blood components and cell growth factors within 14 days before enrollment is not allowed): Absolute neutrophil count ≥1.5×10⁹/L; Platelets ≥80×10⁹/L; Hemoglobin ≥8g/dL; Total bilirubin ≤1.5×ULN (upper limit of normal); ALT (alanine aminotransferase) and AST (aspartate aminotransferase) ≤2.5×ULN (for patients with liver metastasis, ≤5×ULN); Serum creatinine ≤1.5×ULN, and estimated glomerular filtration rate ≥50ml/min; International Normalized Ratio (INR) ≤1.5 or activated partial thromboplastin time (APTT) ≤1.5×ULN; • Good compliance and willingness to cooperate with follow-up. Exclusion Criteria: * Unable to comply with the study protocol or procedures; * Previous treatment with TAS-102 or vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) (e.g., anlotinib, apatinib, etc.); * Participation in other drug clinical trials within 4 weeks before enrollment; * Have received or is currently receiving other systemic anti-tumor treatments within 4 weeks prior to enrollment; * Patients with currently uncontrolled hypertension (defined as systolic blood pressure \>140 mmHg and/or diastolic blood pressure \>90 mmHg) despite medication; * Patients with current diseases or conditions that affect drug absorption, or patients unable to take oral medications; * Patients with active gastrointestinal diseases such as active gastric and duodenal ulcers, ulcerative colitis, active bleeding from unresected tumors, or other conditions judged by the investigator to potentially cause gastrointestinal bleeding or perforation; * History of arterial thrombosis or deep vein thrombosis within 6 months before enrollment; * Patients with evidence or medical history of significant bleeding tendency within 2 months before enrollment, such as melena, hematemesis, hemoptysis, fecal occult blood test (FOBT) result of ++ or above (for patients with FOBT result of + and existing primary lesions, gastroscopy must be performed to rule out bleeding or ulcers before enrollment); * History of stroke and/or transient ischemic attack within 12 months before enrollment; presence of cardiovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe/unstable angina pectoris, or coronary artery bypass grafting within 6 months before enrollment; congestive heart failure of New York Heart Association (NYHA) class \>2; ventricular arrhythmias requiring medication; left ventricular ejection fraction (LVEF) \<50% (confirmed by echocardiography); * History of other malignant tumors within the past 5 years, except for fully treated basal cell carcinoma or squamous cell carcinoma of the skin, carcinoma in situ of organs such as the cervix, early non-invasive lung cancer, and non-muscle-invasive bladder cancer; * Clinically uncontrolled active infections, such as acute pneumonia, active hepatitis B or C (for patients with a history of hepatitis B virus infection, regardless of medication control, hepatitis B virus DNA ≥1×10⁴ copies/mL or \>2000 IU/mL); * Pregnant women (positive pregnancy test before medication administration) or lactating women; * Urinalysis showing urine protein ≥2+, or 24-hour urine protein quantitation \>1.0g; * Patients deemed unsuitable for enrollment in this study by the investigator.