Safety and Efficacy of IB-FOLFIRI in BRAF V600E-Mutant Metastatic Colorectal Cancer

Inclusion Criteria: * Age ≥18 years and ≤75 years * Histologically confirmed metastatic colorectal adenocarcinoma * BRAF V600E mutation confirmed by tissue pathology or ctDNA testing (PCR or NGS) * Disease progression after at least one line of treatment: FOLFOX/XELOX (oxaliplatin-based doublet) ± bevacizumab or FOLFOXIRI (irinotecan-based triplet) ± bevacizumab. Note: Irinotecan must not have failed during prior treatment, and disease must not have progressed within three months of stopping treatment * Patients who have received first-line treatment with cetuximab combined with a BRAF inhibitor (e.g., encorafenib, dabrafenib, vemurafenib) are allowed * At least one measurable lesion according to RECIST v1.1 criteria * Adequate hematologic unction: Platelets \> 90 × 10⁹/L; Hemoglobin \> 100 g/L; White blood cells \> 3 × 10⁹/L; Neutrophils \> 1.5 × 10⁹/L; Adequate liver function; Total bilirubin ≤ 1.5 × ULN; AST and ALT ≤ 2.5 × ULN (≤ 5 × ULN if liver metastases present); Alkaline phosphatase ≤ 2.5 × ULN; No ascites; Coagulation: PT ≤ 1.5 × ULN, INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN, Albumin ≥ 30 g/L * Adequate renal function: CrCl ≥ 50 mL/min or serum creatinine ≤ 1.5 × ULN * Liver function Child-Pugh class A * ECOG performance status 0-1 * Expected survival \> 3 months * Signed written informed consent * Willing and able to comply with follow-up until death, study completion, or study termination * For women of childbearing potential: Negative serum pregnancy test within 14 days prior to treatment; Willing to use medically accepted contraception during the study and for 3 months after the last dose * For male participants with partners of childbearing potential: Must have undergone surgical sterilization, or use effective contraception during the study and for 3 months after the last dose Exclusion Criteria: * KRAS or NRAS mutation * MSI-H/dMMR patients * Prior treatment with PD-1, PD-L1, or CTLA-4 inhibitors * Known contraindications to irinotecan at the planned dose * Use of systemic immunosuppressive drugs within 1 week prior to treatment * Active autoimmune disease requiring treatment, or history of such disease within the past 2 years * Known primary immunodeficiency * History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation * Retinal vein occlusion or risk factors for retinal vein occlusion (e.g., uncontrolled glaucoma or high intraocular pressure) * History of acute or chronic pancreatitis * Chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory, immunosuppressive therapy, or surgery) within 12 months prior to enrollment * Gastrointestinal disorders that may significantly affect oral drug absorption (e.g., severe GI ulcers, uncontrolled vomiting, malabsorption syndrome, short bowel syndrome) * Neuromuscular diseases associated with elevated CK (e.g., inflammatory myopathy, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy) * Residual ≥Grade 2 toxicity from prior anti-tumor therapy (excluding ≥Grade 2 alopecia or neuropathy) * History of HIV infection * History of Gilbert's syndrome * Interstitial pneumonia or extensive symptomatic interstitial pulmonary fibrosis * Severe uncontrolled systemic comorbidities * Severe cardiovascular disease, including: * Stroke within 6 months prior to enrollment * Myocardial infarction within 6 months prior to enrollment * Hypertension not controlled with appropriate medications * Unstable angina * Congestive heart failure (NYHA class 2-4) * Cardiac arrhythmias requiring treatment * Current or prior central nervous system disease, including: Primary brain tumor; Epilepsy not controlled by standard treatment; Any brain metastases or history of stroke * Other uncontrolled comorbidities, including active bleeding, uncontrolled infection or non-malignant medical conditions that could be worsened by study therapy, or uncontrolled psychiatric/social conditions * History of other malignancies within the past 5 years (except for curatively treated basal cell carcinoma, cervical carcinoma in situ, or thyroid cancer) * Allergy to any study drug * Pregnant or breastfeeding women * Women of childbearing potential (last menstrual period \<2 years) or men who refuse to use effective non-hormonal contraception (IUD, barrier method plus spermicide, or sterilization) * Inability or unwillingness to comply with study protocol * Any other disease, metastatic lesion-related functional impairment, or suspicious findings on physical examination that may indicate contraindication to study drug use or place the patient at high risk of treatment-related complications.