Introduction Lower gastrointestinal bleeding (LGIB) is a common cause of emergency hospitalization and may require readmission for re-bleeding. A novel adhesive endoscopic hemostatic powder (UI-EWD/NexpowderTM, Nextbiomedical, Incheon, South Korea) has been developed and recently utilized for LGIB hemostasis. The aim of the current study was to assess the efficacy and safety of UI-EWD as a rescue therapy for the treatment of refractory LGIB. Methods In this study, a total of 59 consecutive patients with LGIB who experienced initial hemostasis failure with conventional endoscopic therapy were enrolled into this multicenter single-arm study. These patients subsequently underwent UI-EWD application for the refractory LGIB hemostasis. We evaluated the success rate of hemostasis, re-bleeding rate within 30 d, and adverse events related to UI-EWD. Results UI-EWD was successfully administered to the bleeding sites in all enrolled refractory bleeding patients. Hemostasis was achieved in the entirety of the 59 patients (100%). The cumulative re-bleeding rate within 30 d was 8.5% (5/59). There were no UI-EWD-related adverse events, such as perforation nor embolism. Conclusion Based on our results, the utilization of UI-EWD demonstrated a remarkable success rate in achieving hemostasis for refractory LGIB, while also exhibiting promising outcomes in reducing the re-bleeding rate within a 30-day period. Particularly, UI-EWD exhibits a favorable safety profile across all segments of the colon in cases of refractory LGIB.