Inclusion Criteria

Main selection criteria:

1. Histological proven CRC with completely resectable metachronous or synchronous liver
metastases (as judged by the treating surgeon).

2. Patients must have undergone complete resection (R0) of the primary tumor at least 4
weeks before randomization. Or in case of synchronous disease with intact primary;
the primary tumor have to be R0 resectable together with the liver metastases and the
patient has a non-obstructive primary tumor and is able to receive preoperative
chemotherapy before surgery. Synchronous rectal primary is not allowed.

3. Measurable hepatic disease by Response Evaluation Criteria in Solid Tumors (RECIST
version 1.1).

4. No evidence of extra-hepatic metastasis of CRC.

5. Patients must be from 18 to 75 years.

6. ECOG Performance status ≤ 1

7. No previous chemotherapy for metastatic disease. Radiotherapy alone is allowed if
given pre or post protocol treatment.

8. Previous adjuvant chemotherapy for primary CRC is allowed if completed at least 6
months before inclusion in this study.

9. All the following tests should be done within 4 weeks prior to randomization

- Absolute neutrophil count > 1.5 x 109/L, platelets > 100 x 109/L, and hemoglobin
> 9 g/dL or 5.59 mmol/l.

- Serum creatinine less than 1.5 times the upper limit of normal (ULN) (to exclude
severe renal impairment); no significant proteinuria (urine dipstick for
proteinuria ³ 2+. If urine dipstick is ³ 2+, 24-hour urine must demonstrate £ 1
g of protein in 24 hours for patient to be eligible).

- Absence of major hepatic insufficiency (bilirubin < 1.5 x ULN and aspartate
aminotransferase (ASAT)/alanine aminotransferase (ALAT) < 5 x ULN).

- Patients not receiving therapeutic anticoagulation must have an INR < 1.5 ULN
and aPTT < 1.5 ULN within 7 days prior to registration. The use of full dose
anticoagulants is allowed as long as the INR or aPTT is within therapeutic
limits (according to the medical standard in the institution) and the patient
has been on a stable dose for anticoagulants for at least two weeks at the time
of registration.

10. No pregnancy or breast feeding. Negative serum pregnancy test within 7 days of
starting study treatment in pre-menopausal women and women < 1 year after the onset
of menopause is required before entering in the trial. Note: a negative test has to
be reconfirmed by a urine test, should the 7-day window be exceeded.

11. Adequate contraception is required during and for 3 months after study treatment for
both male and female patients if the risk of conception exists.

12. No major surgical procedure, open biopsy, or significant traumatic injury within 4
weeks prior to randomization.

13. No previous exposure to VEGF/VEGFR-targeting therapy within the last 12 months.

14. No thrombosis or severe bleeding within 6 months prior to entry into the study
(except for bleeding of the tumor before its surgical resection) and no evidence of
bleeding diathesis or coagulopathy.

15. Absence of peripheral neuropathy NCI CTCAE-grade ≥ 1, active inflammatory bowel
disease or other bowel disease causing chronic diarrhea (defined as > 4 loose stools
per day), serious wound complications, ulcers, or bone fractures.

16. No evidence of any other disease, metabolic dysfunction, physical examination finding
or laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug or puts the patient at high risk
for treatment-related complications.

17. No concomitant treatment with ASS > 325 mg or NSAIDs, known to inhibit platelet
function, sorivudin or analog compounds or preparations of St. John's wort.