Fruquintinib Plus Anti-EGFR Antibody for Third-Line Treatment of RAS Wild-Type mCRC

Inclusion Criteria: 1. Age 18-75 years, inclusive. 2. Fully informed about the study and willing to sign written informed consent. 3. Histologically confirmed metastatic or advanced colorectal adenocarcinoma. 4. Tumor confirmed as NRAS, KRAS, and BRAF wild-type. 5. At least one measurable lesion according to RECIST 1.1 criteria. 6. ECOG performance status of 0-1. 7. Estimated life expectancy ≥ 12 weeks. 8. Prior treatment with oxaliplatin- and irinotecan-based therapy, or failure of at least two prior standard regimens. 9. Prior treatments must have included fluoropyrimidine, oxaliplatin, and irinotecan (with or without bevacizumab or cetuximab). 10. Treatment failure defined as disease progression during therapy or within 3 months after last treatment, or intolerance to toxicity. 11. Recurrence within 6 months after adjuvant/neoadjuvant therapy is considered as first-line failure. 12. Adequate organ function within 7 days prior to enrollment: * ANC ≥ 1.5 × 10⁹/L * Platelets ≥ 80 × 10⁹/L * Hemoglobin ≥ 8 g/dL * Total bilirubin ≤ 1.5 × ULN * AST/ALT ≤ 2.5 × ULN (≤ 5 × ULN in liver metastasis) * Serum creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 50 mL/min * INR ≤ 1.5 or APTT ≤ 1.5 × ULN 13. No receipt of blood products or growth factors within 14 days prior to enrollment. 14. Able and willing to comply with study procedures and follow-up. Exclusion Criteria: 1. Unable or unwilling to comply with the study protocol. 2. Prior treatment with VEGFR tyrosine kinase inhibitors (e.g., regorafenib). 3. Participation in another clinical trial within 4 weeks. 4. Systemic anticancer therapy within 4 weeks before enrollment. 5. Uncontrolled hypertension (SBP \> 140 mmHg or DBP \> 90 mmHg). 6. Any condition that affects drug absorption or inability to take oral medication. 7. Active gastric or duodenal ulcer, ulcerative colitis, or tumor-related active bleeding. 8. Positive fecal occult blood (≥ ++) without endoscopic exclusion of bleeding. 9. Arterial or deep venous thrombosis within 6 months. 10. Significant bleeding within 2 months (melena, hematemesis, hemoptysis). 11. Stroke or transient ischemic attack within 12 months. 12. Significant cardiovascular disease: * Acute myocardial infarction within 6 months * Severe or unstable angina * Heart failure NYHA class \> II * Clinically significant arrhythmia requiring treatment * LVEF \< 50% 13. History of other malignancies within 5 years (except adequately treated in-situ cancers or early non-invasive cancers). 14. Uncontrolled active infection, including HBV or HCV (HBV DNA ≥ 1×10⁴ copies/mL or \>2000 IU/mL). 15. Pregnant or breastfeeding women. 16. Urine protein ≥ 2+ or 24-hour urine protein \> 1.0 g. 17. HIV-positive individuals. 18. Any condition that, in the investigator's judgment, makes the patient unsuitable for the study.