Bevacizumab, an anti-angiogenic agent, plus fluorouracil based chemotherapy is considered a new standard for the treatment of metastatic colorectal cancer. Contrast-enhanced ultrasound with gas-encapsulated microbubbles can be used to assess tumour vascularity, particularly hepatic metastases, and may become a useful tool for monitoring anti-angiogenic therapies. The aim of this prospective, multicenter, non-randomized study is to evaluate the usefulness of hepatic contrast-enhanced ultrasound to predict response to bevacizumab based chemotherapy in patient with metastatic colorectal cancer. The primary objective of this study is to compare the functional vascular changes related to bevacizumab based chemotherapy and evaluated by hepatic contrast-enhanced ultrasound with classic RECIST criteria. The secondary objectives are to do a characterization of the pharmacokinetic of bevacizumab, to explore the pharmacodynamic effects of bevacizumab on functional vascular changes of hepatic metastases evaluated by hepatic contrast-enhanced ultrasound and to analyze the possible relationships between treatment efficacy or toxicity and constitutional gene polymorphisms linked to the bevacizumab.

Inclusion Criteria:

• Histologically confirmed colorectal tumor
• first line treatment by a bevacizumab based chemotherapy
• Target hepatic metastases of size lower than 5 cm and higher than 5 mm detected by conventional ultrasonography and CT or MRI
• Life expectancy > 2 months
• OMS status =< 2
• Major surgery, open biopsy, or significant traumatic injury within 28 days prior to Day 0
• informed consent signed

Exclusion Criteria:

• no target hepatic lesion detected by conventional ultrasonography
• Prior bevacizumab treatment
• Prior chemotherapy treatment for advanced disease
• Clinically significant cardiac disease (e.g. myocardial infarction or stroke within 12 months, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure not well controlled with medication, endocarditis and prosthetic valve) and any contraindications in sulphur hexafluoride administration
• Blood pressure >= 180/110 mmHg
• Daily and chronic treatment by aspirin or AINS
• Anticipation of need for major surgical procedure within 7 days prior day 0
• Urine protein > 1g/24 Hours
• Any contraindication in enhancing bevacizumab treatment
• Serious, uncontrolled, concurrent infection(s) or illness(es)
• pregnant and lactating woman