This work presents a new methodology to assess the outward connectivity among regional economies in the EU and derives policy lessons for the design of regional innovation and competitiveness-enhancing strategic frameworks, with particular reference to research and innovation strategies for smart specialisation (RIS3). We study the network of inter-regional trade flows in the EU25 in the year 2007. We measure both global properties of the network and centrality indicators describing the position of individual regions within the system. Specific policy implications in the context of RIS3 are derived in the case of the Spanish region of Andalusia. We show the potential of the methodology for providing a new family of indicators of the external connectivity of regional economies that can be used by regions wishing to develop their own RIS3 for 2014-2020, as required by the EU in the context of the new cohesion policy framework.