Several high-tech manufacturing technologies are emerging to meet the demand for mass customized products. These technologies include configurable robots, augmented reality and the Internet-of-Things. Manufacturing enterprises can leverage these new technologies to pursue increased flexibility, i.e., the ability to perform a larger variety of activities within a shorter time. However, the flexibility offered by these new technologies is not fully exploited, because current operations management techniques are not dynamic enough to support high variability and frequent change. The HORSE Project investigated several of the new technologies to find novel ways to improve flexibility, as part of the Horizon 2020 research and innovation program. The purpose of the project was to develop a system, integrating these new technologies, to support efficient and flexible manufacturing. This article presents the core result of the project: a reference architecture for a manufacturing operations management system. It is based on the application and extension of business process management (BPM) to manage dynamic manufacturing processes. It is argued that BPM can complement current operations management techniques by acting as an orchestrator in manufacturing processes augmented by smart technologies. Building on well-known information systems’ architecting frameworks, design science research is performed to determine how BPM can be applied and adapted in smart manufacturing operations. The resulting reference architecture is realized in a concrete HORSE system and deployed and evaluated in ten practical cases, of which one is discussed in detail. It is shown that the developed system can flexibly orchestrate the manufacturing process through vertical control of all agents, and dynamic allocation of agents in the manufacturing process. Based on that, we conclude that BPM can be applied to overcome some of the obstacles toward increased flexibility and smart manufacturing.