Objectives. To compare usual care, inreach consisting of one-on-one education, mailed outreach offering a fecal immunochemical test (FIT), and a combination of outreach and inreach for promoting colorectal cancer (CRC) screening.Methods. We conducted a 4-arm randomized controlled trial from 2015 to 2018 at a US federally qualified health center near the California-Mexico border primarily serving low-income Hispanics/Latinos. A total of 673 individuals aged 50 to 75 years not up to date with screening were assigned to 1 of the 4 intervention groups. The primary outcome was CRC screening through 6 months follow-up.Results. A total of 671 patients were included in intention-to-screen analyses. Their mean age was 59.9 years, 48.9% were male, and 86.3% were primarily Spanish-speaking. Screening was 27.5% for usual care (95% confidence interval [CI] = 0.21, 0.34), 52.7% for inreach (95% CI = 0.45, 0.60), 77.2% for outreach (95% CI = 0.71, 0.83), and 78.9% for combination of inreach and outreach (95% CI = 0.73, 0.85; P < .001 for all comparisons except P = .793 for outreach vs combination).Conclusions. Among individuals at high risk for noncompletion, inreach with one-on-one education nearly doubled, and outreach offering mailed FIT alone or in combination with inreach nearly tripled screening compared with usual care. Mailed FIT outreach was superior to inreach for promoting screening.