Colorectal cancer (CRC) in pregnancy is rare and often presents at a late stage due to the masking of signs by pregnancy. A typical chemotherapeutic regimen for stage III and IV CRC comprised 5-Fluorouracil (5-FU) and oxaliplatin. The treatment of CRC during pregnancy is complicated owing to the potential risk of teratogenicity with chemotherapy, especially in the first trimester. Data suggest that the administration of chemotherapy beyond the first trimester may be relatively safe. Previous reports have shown success with the use of FOLFOX (folinic acid, 5-FU, oxaliplatin) and FOLFIRI (folinic acid, 5-FU, irinotecan) during pregnancy. Moreover, neoadjuvant FOLFOXIRI (folinic acid, 5-FU, oxaliplatin, irinotecan) resulted in improved outcomes when compared to standard preoperative chemoradiotherapy in the treatment of locally advanced and metastatic CRC. The use of FOLFOXIRI in pregnancy is not currently documented, and therefore, the outcomes of using this chemotherapeutic regimen are unclear. The aim of this case report was to demonstrate the use of FOLFOXIRI in pregnancy. A retrospective chart review was performed to assess the clinical course and fetal outcome of 2 patients presented in this case report. FOLFOXIRI was initiated in two pregnant women with nonmetastatic and metastatic CRC, resulting in successful delivery of healthy infants. FOLFOXIRI is an effective chemotherapy regimen for the treatment of advanced CRC and may be used during the second and third trimesters of pregnancy.