This is multinational, double-blind, two-arm, parallel, randomized Phase 3 comparison study evaluating the efficacy and safety of TAS-102 vs. placebo in patientws with refractory metastatic colotrectal cancer. Patients will be randomly assigned (2:1) to TAS-102 (experimental arm) or placebo (control arm). Randomization will take place once the consented patient has completed all the necessary Baseline procedures and is deemed eligible for study entry. Treatment assignement will be done centrally using a dynamic allocation method (biased coin) via an Interactive Voice/Web Response System (IXRS) stratified by:

KRAS gene type (wild, mutant)

Time since diagnosis of first metastasis

Geographical region (Region 1:Asia/Japan, Region 2: Western/USA and Europe