Background Increased incidence and life expectancy have resulted in a growing population of patients with metastatic breast cancer, and these patients experience high rates of morbidity and premature mortality. Increased physical activity (PA) is consistently associated with improved health and disease outcomes among early-stage survivors. However, there is a paucity of research on PA in patients with metastatic breast cancer, and existing PA interventions have exhibited low feasibility because of their focus on intense PA and/or requirement of on-site visits. Mobile health (mHealth)–based PA interventions may be particularly useful for patients with metastatic breast cancer because they allow for remote monitoring, which facilitates individual tailoring of PA recommendations to patients’ abilities and may minimize participant burden. However, no studies have examined mHealth PA interventions in patients with metastatic breast cancer. Objective We aim to address these critical research gaps by testing a highly tailored technology-based intervention to promote PA of any intensity (ie, light, moderate, or vigorous) by increasing daily steps in patients with metastatic breast cancer. The primary aim of this study is to test the feasibility and acceptability of the Fit2ThriveMB intervention. We will also examine outcome patterns suggesting the efficacy of Fit2ThriveMB on symptom burden, quality of life, and functional performance. Methods The Fit2ThriveMB trial is a two-arm pilot randomized controlled trial that will compare the effects of a smartphone-delivered, home-based PA intervention and an attention-control education condition on PA and quality of life in low-active female patients with metastatic breast cancer. A subsample (n=25) will also complete functional performance measures. This innovative trial will recruit 50 participants who will be randomized into the study’s intervention or control arm. The intervention will last 12 weeks. The Fit2ThriveMB intervention consists of a Fitbit, coaching calls, and the Fit2ThriveMB smartphone app that provides self-monitoring, a tailored goal-setting tool, real-time tailored feedback, app notifications, and a group message board. Assessments will occur at baseline and post intervention. Results The Fit2ThriveMB study is ongoing. Data collection ended in February 2021. Conclusions Data from this study will provide the preliminary effect sizes needed to assemble an intervention that is to be evaluated in a fully powered trial. In addition, these data will provide essential evidence to support the feasibility and acceptability of using a technology-based PA promotion intervention, a scalable strategy that could be easily integrated into care, among patients with metastatic breast cancer. Trial Registration ClinicalTrials.gov NCT04129346; https://clinicaltrials.gov/ct2/show/NCT04129346 International Registered Report Identifier (IRRID) DERR1-10.2196/24254