FOLFOXIRI With or Without Bevacizumab as First-line Treatment for Unresectable Liver-only Metastatic Colorectal Cancer Patients With RAS Mutation-type

Inclusion Criteria:

1. Willing and able to provide written informed consent
2. Histological or cytological documentation of adenocarcinoma of the colon or rectum.
3. Male or female subjects \> 18 years \< 70 of age.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. There must be documentation by CT scan, MRI, or intraoperative palpation that the patient has evidence of metastases confined to the liver.
6. The liver metastases must have been assessed by multidisciplinary team including hepatic surgeon approved to participate in the study to be unresectable based on at least one of the four criteria: 1. All of the liver metastases can not be completed resected with negative margins; 2. No ability to preservation of two contiguous hepatic segments; 3. No ability to preservation of adequate vascular inflow and outflow as well as biliary drainage; 4. Complete resection would require greater than 70% of the liver parenchyma to be removed.
7. The colorectal primary tumor or metastatic tumor must be determined to be KRAS (exon 2 at codon 12 and 13; exon 3 at codon 59 and 61; exon 4 at codon 117 and 146) or NRAS (exon 2 at codon 12 and 13; exon 3 at codon 59 and 61; exon 4 at codon 117 and 146) mutation-type.
8. Primary tumor and regional nodes were resected with clear surgical margins or; unresected primary tumor with plan to radical resect the primary tumor.
9. No previous any systemic anticancer therapy for metastatic disease (adjuvant chemotherapy for non-metastatic disease is allowed if terminated more than 6 months ago).
10. Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: Hemoglobin (Hb) ≥ 90g/ L, absolute neutrophil count (ANC) ≥ 1.5×109/ L, platelet count ≥ 100×109/ L; Total bilirubin ≤ 1.5×the upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 ×ULN; Serum creatinine ≤1.5×the ULN.

Exclusion Criteria:

1. Any evidence of extrahepatic metastases, lymph node (including portal lymph nodes) metastases and primary tumor recurrence.
2. Previous hepatic resection and/or ablation, hepatic arterial infusion therapy, radiation therapy to the liver.
3. Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization.
4. Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
5. Heart failure grade III/IV (NYHA-classification).
6. Unresolved toxicity higher than CTCAE v.4.0 Grade 1 attributed to any prior therapy/procedure.
7. Subjects with known allergy to the study drugs or to any of its excipients.
8. Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
9. Breast- feeding or pregnant women
10. Lack of effective contraception.