Background: Patients with mCRC generally have a limited life expectancy, however, a small number of patients with liver-only mCRC could be cured following metastasectomy. In highly selected patients with mCRC, FOLFOXIRI (5FU, oxaliplatin, and irinotecan) plus bev results in high response rates. However, very limited evidence is available about efficacy of this regimen in real-world patients with liver-only mCRC. Furthermore, there is paucity of biomarkers that predict liver metastasectomy in such patients. The current study aims a) to evaluate rate of conversion from unresectable to resectable liver metastases in real-world patients with liver-only mCRC following FOLFOXIRI-bev, b) to identify predictive markers including an early PET-FDG response that correlate with curative surgery, & c) to determine disease control rate, overall survival, quality of life, treatment toxicities, and cost-effectiveness of surgery. Methods: In this pragmatic phase 2 study, 37 patients with liver-only unresectable mCRC who are deemed eligible for FOLFOXIRI-bev by their oncologist will be recruited at the two major cancer centers in Saskatchewan. Patients will receive FOLFOXIRI-bev every two weeks for a total of 12 cycles and will undergo periodic imaging tests. The resectability of liver metastases will be determined by a multidisciplinary team. For those patients who are not able to undergo a curative surgery, a doublet chemotherapy regimen ±bev will be continued at the discretion of treating oncologist. . The prognostic and predictive value of mutations in specific genes involved in cell proliferation, cell death resistance, angiogenesis, and invasion in colorectal cancer along with the relationship between the abundance and characteristics of exRNA and conversion rate and survival will be assessed. Logistic regression and Cox proportional analyses will be performed to assess correlation between an eight-week FDG-PET/CT response to chemotherapy and other biomarkers and rate of removal of metastases and survival, respectively. This pragmatic study will help to determine conversion rate in real-world patients with FOLFOXIRI plus bev and role of early FDG-PET/CT scan response and other biomarkers in predicting metastasectomy along with cost-effectiveness of this approach. Clinical trial information: NCT03401294