Inclusion Criteria:

1. Non-resectable, histologically confirmed, synchronous or metachronous colorectal
liver metastases.

2. Non-resectability will be documented by a local multidisciplinary tumour board with
participation of a surgeon experienced in liver surgery. Patients can be enrolled if
they

a) are technically non-resectable (locally determined by a multidisciplinary team
discussion based on remaining functional liver tissue after resection, i.e.

i) involvement of both portal veins, all hepatic veins, portal vein of the liver lobe
and hepatic veins draining the segments of the other liver lobe, or ii) other reasons
for less than 30% remaining functional liver tissue after resection) and / or b) have
≥ 5 liver metastases and / or c) are regarded as non-resectable for other reasons
(description necessary)

3. Patients with simultaneous liver metastases are eligible,

1. if the primary tumour was resected at least 1 month prior to chemotherapy or

2. all of the following conditions apply:

i) the primary tumour is clearly resectable, ii) no radiation therapy is planned,
iii) liver resection is planned before resection of the primary or at the same
operation as the resection of the primary, iv) no two-stage liver resection is
planned, and v) all efforts were made to exclude additional distant metastases.

4. WHO PS ≤ 1

5. Written informed consent

6. Adequate bone marrow function, liver function (neutrophils > 1.5 x 109/l; platelets >
100 x 109/l; haemoglobin > 5.0 mmol/l [8.0 g/dl]; bilirubin ≤ ULN or ≤ 1.5 x ULN and
not increasing more than 25 % within the last 4 weeks; SGOT and SGPT < 5 x UNL)

7. Age ≥ 18 years

Exclusion Criteria:

1. Any evidence of extrahepatic metastases, distant lymph node metastases and primary
tumour recurrence

2. Patients with b-raf mutations

3. Prior systemic antitumour therapy with anti- EGFR-, antiangiogenic drugs or with
chemotherapy (except adjuvant chemotherapy for stage II / III with an interval of ≥ 6
months or in combination with radiation as radio sensitizer)

4. Radiotherapy or major abdominal or thoracic surgery (excluding diagnostic
interventions or venous port implantation) ≤ 4 weeks before study entry

5. Renal insufficiency with serum creatinine ≥ 1.5 x UNL. If serum creatinine is between
1.0 and 1.5 x UNL, the creatinine clearance according to the Cockroft-Gault formula
should be ≥ 60 ml/min

6. Hypertension with an arterial blood pressure > 150/90 mmHg

7. Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or
IV, unstable angina pectoris, history of myocardial infarction within the last 12
months, significant arrhythmias

8. Known proteinuria > 1 g/day (to be tested if proteinuria more than 1+ in the urinary
dipstick analysis)

9. Peripheral neuropathy > CTC grade I

10. Concurrent systemic immune therapy, chemotherapy, hormone therapy, or patients
receiving immune suppressive treatment (i.e. for transplantation, severe
rheumatologic disease)

11. Participation in clinical trials with investigational agents within 30 days before
start of the treatment in study

12. Active treatment of

1. peptic ulcers or bleeding erosive esophagitis / gastritis within 3 months before
study

2. stroke, transient ischemic attack or symptomatic pulmonary embolism within 6
months before study

3. deep vein thrombosis within 4 weeks before study

13. Inflammatory bowel disease

14. History of other malignancies, from which the patient is not 5 years disease free,
with the exception of colorectal cancer, or adequately treated basal cell or squamous
cell carcinoma of skin or in-situ cervical cancer within 5 years before study

15. History of brain metastases

16. History of severe psychiatric illness

17. Active drug- or alcohol abuse

18. Known hepatitis B or C or HIV infection

19. Breast- feeding or pregnant women

20. Lack of effective contraception (for male and female patients, during study until 6
months after end of treatment)

21. Known intolerance to one of the following drugs: cetuximab, bevacizumab, oxaliplatin,
irinotecan, 5-FU, folinic acid