The purpose of this study is to assess 2 different doses of onvansertib to select the lowest dose that is maximally effective, and to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of onvansertib in combination with FOLFIRI + bevacizumab or FOLFOX + bevacizumab in patients with KRAS or NRAS-mutated metastatic colorectal cancer (CRC) in the first-line setting.

Inclusion Criteria:

• Histologically confirmed metastatic colorectal cancer.
• Documented KRAS or NRAS mutation.
• No previous systemic therapy in the metastatic setting.
• Participants must be willing to submit archival tissue or undergo fresh biopsy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Women of childbearing potential must use contraception or take measures to avoid pregnancy.
• Imaging computed tomography (CT) or magnetic resonance imaging (MRI) of chest/abdomen/pelvis and other scans as necessary to document all sites of disease performed within 28 days prior to the first dose of onvansertib.
• Must have acceptable organ function

Exclusion Criteria:

• Concomitant KRAS or NRAS and BRAF-V600 mutation or microsatellite instability high/deficient mismatch repair.
• Prior treatment with a VEGF inhibitor, including bevacizumab or biosimilars.
• Previous oxaliplatin treatment within 12 months prior to randomization, when arm open.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency.
• Anticancer chemotherapy or biologic therapy administered within 28 days prior to the first dose of study drug.
• Untreated or symptomatic brain metastasis.
• Gastrointestinal (GI) disorder(s) that would significantly impede the absorption of an oral agent.
• Unable or unwilling to swallow study drug.
• Uncontrolled intercurrent illness.
• Known hypersensitivity to fluoropyrimidine or leucovorin, irinotecan, or oxalipatin.
• Abnormal glucuronidation of bilirubin; known Gilbert's syndrome.
• Use of strong CYP3A4 or CYP2C19 inhibitors or strong CYP3A4 inducers.
• QTc >470