The Efficacy of Bevacizumab Combined With m-FOLFOXIRI in Borderline Resectable Colorectal Liver Metastases

Inclusion Criteria: 1. Histologically proven diagnosis of colorectal cancer. 2. Borderline resectable liver metastases of colorectal cancer considered to have poor-risk disease not deemed to be suitable for upfront resection if they had one or more of the following features assessed by a local multidisciplinary team: more than four metastases, any liver lesion with diameter \>5 cm, location and distribution of metastatic disease within the liver unsuitable for resection with clear margins (e.g. involvement of both lobes of liver, invasion of intrahepatic vascular structures), extent of liver involvement precluding resection with adequate post-resection residual liver parenchyma volume for viable liver function in the immediate postoperative period, and inability to retain adequate vascular inflow and outflow to maintain viable liver function. 3. At least one measurable lesion according to RECIST criteria. 4. Age 20-75 years. 5. ECOG performance \< 1 if age \< 70 years, ECOG PS = 0 if age = 70-75 years. 6. Life expectancy of at least 12 weeks. 7. Neutrophils ≥1.5 x 109/L, Platelets≥ 100 x 109/L, Hgb ≥10 g/dl. 8. Total bilirubin ≤1.5 time the upper-normal limits (UNL) of the Institutional normal values and ASAT (SGOT) and/or ALAT (SGPT) ≤5 x UNL, alkaline phosphatase ≤5 x UNL. 9. Serum creatinine≤ 1.5 x UNL. 10. Patients discovered to have proteinuria on urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate ≤1 g of protein/24 hr. 11. Written informed consent. Exclusion Criteria: 1. Prior neoadjuvant or adjuvant chemotherapy completed \<6 months. 2. Prior chemotherapy for metastatic disease. 3. Any extrahepatic metastases. 4. History or evidence upon physical examination of CNS disease unless adequately treated (e.g., seizure not controlled with standard medical therapy or history of stroke). 5. Serious, non-healing wound, ulcer, or bone fracture. 6. Evidence of bleeding diathesis or coagulopathy. 7. Uncontrolled hypertension. 8. Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤ 6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication. 9. Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes. 10. Chronic daily treatment with aspirin . 11. Patients with known allergy to Chinese hamster ovary cell proteins, or any of the components of the study medications. 12. Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of sin basal cell carcinoma or cervical cancer in situ. 13. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study. 14. Other severe systemic diseases without stable medical control. 15. Pregnant or lactating women.