。
What's got her so worked up?
Literal
She [topic-は] what [object-を] is-being-irritated [casual question-の]
いらいら is one of Japanese's many 擬態語 (state mimetics) — a doubled mimetic capturing the prickly, fidgety feel of irritation rather than a literal sound. Add する and it becomes a verb. The を here is colloquially marking the source of the irritation; いらいらする is normally intransitive (taking に or で for cause), so this construction lands with a slightly insistent 'what's she stewing over?' tone. Final の adds the casual demand for an explanation, the same particle a parent might use when asking a child why they look upset.