• Histologically confirmed colorectal adenocarcinoma

• Imaging or pathological confirmation of liver metastases

• The multidisciplinary team determined that the liver metastases were unresectable, defined as (i) ≥5 metastases; (ii) inability to perform R0 resection; (iii) insufficient volume of liver expected to remain after resection; (iv) failure to preserve all 3 hepatic veins after resection, failure to ensure that blood flow to and from the liver and bile ducts can be preserved, and failure to preserve 2 adjacent liver segments. If any of the above criteria are met, it can be considered as initially unresectable liver metastases.

• Patients with mutated RAS and BrafV600E

• No previous treatment for liver metastases, including chemotherapy, surgery, radiotherapy, transarterial chemoembolization (TACE) and targeted therapy

• No extrahepatic metastases confirmed by CT, MRI, or PET/CT (if necessary) (consider enrollment if there is a lung or lymph node lesion less than 10 mm and metastases are difficult to identify)

• Normal hematological function (platelets \>90×109/L; white blood cells \>3×109/L; neutrophils \>1.5×109/L)

• Serum bilirubin ≤ 1.5 times the upper limit of normal value (ULN), transaminases ≤ 5 times ULN

• No ascites, normal coagulation function, albumin ≥35g/L

⁃ Liver function Child-Push grade A

⁃ Serum creatinine less than upper limit of normal (ULN) or calculated creatinine clearance \>50 ml/min (using Cockcroft-Gault formula)

⁃ ECOG score 0-1

⁃ Life expectancy \> 3 months

⁃ Signed written informed consent