This double blind, randomized phase II trial will investigate whether the addition of tocotrienol will improve the effect and lower the toxicity of standard chemotherapy and bevacizumab. Half of the patients will receive tocotrienol and the other half placebo. Treatment is planned for a period of maximum six months and will be discontinued earlier in case of progression or unacceptable toxicity.

Inclusion Criteria:

• Histopathologically verified adenocarcinoma of the colon or rectum

• Metastatic disease

• Planned treatment with FOLFOX or capecitabine combined with bevacizumab

• Evaluable disease according to RECIST 1.1

• Performance status 0-2

• Expected survival ≥ 3 months

• Patient acceptance to collection of blood samples for translational research

• Age ≥ 18 years

• Contraception during and 6 months after last dose for women of childbearing potential (less than one year amenorrhea and not undergone hysterectomy, bilateral salpingectomy or bilateral oophorectomy) and for male patients with a fertile partner. Hormonal contraception, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence is accepted.

• Adequate bone marrow function, liver function, and renal function (within 7 days prior to inclusion):

  • WBC ≥ 3.0 x 109/l or neutrophils (ANC) ≥ 1.5 x 10^9/l
  • Platelet count ≥ 100 x 10^9/l
  • Hemoglobin ≥ 6.0 mmol/l
  • Serum bilirubin ≤ 2.0 x ULN
  • Serum transaminase ≤ 2.5 x ULN
  • Serum creatinine ≤ 1.5 ULN

• Urine dipstick for protein ≤ 2+, if the dipstick shows protein ≥ 2+, 24 hour urine testing must be performed and show protein contents ≤ 1g.

• Written and orally informed consent

Exclusion Criteria:

• Other active malignant disease within 5 years prior to inclusion in the study.
• Other experimental therapy within 28 days prior to treatment initiation.
• Underlying medical disease not adequately treated.
• Surgery, including open biopsy, within 4 weeks prior to first dose of bevacizumab.
• Cerebral vascular attack, transient ischemic attack or subarachnoid hemorrhage within six months before start of treatment
• Bleeding tumor
• Pregnant or breastfeeding women
• Fertile patients not willing to use effective methods of contraception during treatment and for six months after end of treatment.
• Hypersensitivity to one or more active substances or auxiliary substances