Preventive Treatment of Oxaliplatin Induced Peripheral Neuropathy in Metastatic Colorectal Cancer (POLAR-M)

Inclusion Criteria:

* Signed informed consent form before any study related assessments and willing to follow all study procedures.
* Male or female aged \>=18 years.
* Non-resectable metastatic (stage IV) CRC, pathologically confirmed adenocarcinoma of the colon or rectum.
* No prior chemotherapy (within the previous 12 months) and/or biologic/targeted therapy for mCRC.
* Measurable disease according to RECIST 1.1.
* Patient indicated for at least 3 months of oxaliplatin-based chemotherapy (without any pre-planned treatment breaks) and without any clinically observed neurological disorders.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Adequate hematological parameters: hemoglobin \>=100 g/L, absolute neutrophil count (ANC) \>=1.5 x 10\^9 /L, platelets \>=100 x 10\^9 /L.
* Adequate renal function: creatinine clearance \>50 cc/min using the Cockroft and Gault formula or measured.
* Adequate hepatic function: total bilirubin \<=1.5 times the upper limit of normal (ULN) (except in the case of known Gilbert's syndrome); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<=3 times ULN (AST and ALT \<=5 times ULN in case of liver metastases).
* Baseline blood manganese (Mn) level \<2.0 times ULN.
* For patients with a history of diabetes mellitus, HbA1c \<=7%.
* Negative pregnancy test for females of child-bearing potential.
* For men and females of childbearing potential, use of adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) while on study drug and for at least 6 months after completion of study therapy.

Exclusion Criteria:

* Any unresolved toxicity by Common Terminology Criteria for Adverse Events Version (CTCAE v4.03) \> Grade 1 from previous anti-cancer therapy (including radiotherapy), except alopecia.
* Any grade of neuropathy from any cause.
* Any evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, cardiac, unresolved bowel obstruction, hepatic or renal disease).
* Chronic infection or uncontrolled serious illness causing immunodeficiency.
* Any history of seizures.
* A surgical incision that is not healed.
* Significant hemorrhage (\>30 mL/bleeding episode in previous 3 months), hemoptysis (\>5 mL fresh blood in previous 4 weeks) or thrombotic event (including transient ischemic attack) in the previous 12 months if the patient is expected to receive anti-VEGF/VEGFR therapy.
* Known hypersensitivity to any of the components of mFOLFOX6 and, if applicable, biological therapies to be used in conjunction with the chemotherapy regimen or any of the excipients of these products.
* History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within 5 years, unless the patient has been disease free for that other malignancy for at least 2 years.
* Known dihydropyrimidine dehydrogenase deficiency.
* Pre-existing neurodegenerative disease (e.g., Parkinson's, Alzheimer's, Huntington's) or neuromuscular disorder (e.g., multiple sclerosis, amyotrophic lateral sclerosis, polio, hereditary neuromuscular disease).
* Major psychiatric disorder (major depression, psychosis), alcohol and/or drug abuse.
* Patients with a history of second or third degree atrioventricular block or a family heredity.
* A history of a genetic or familial neuropathy.
* Treatment with any investigational drug within 30 days prior to randomization.
* Pregnancy, lactation or reluctance to using contraception.
* Any other condition that, in the opinion of the Investigator, places the patient at undue risk.
* Previous exposure to mangafodipir or calmangafodipir.
* Welders, mine workers or other workers in occupations (current or past) where high manganese exposure is likely.